Frontiers, Not Boundaries

LDT Arrays Bio Markers Mapping Spheroid Array Image Analysis Risk Assessment ISH/IHC Analysis Product Rescue Reports & Publications Integrated 'Omics

Services

MicroMatrices offers a range of molecular profiling technologies designed to unlock the biology contained within fresh/frozen, FFPE, or spheroid/3D clinical or nonclinical tissue samples. Our services can be used singly or in combination to increase resolution in discovery and investigative safety studies.

SpheroMatrices – our proprietary spheroid tissue microarray for obtaining medium-high throughput toxicity/efficacy data from human-relevant organotypic spheroid cultures

The SpheroMatrices® array technology (patent pending) overcomes the challenges of obtaining quantitative data in  3D spheroid/microtissue experiments by aligning all the spheroids within a 96 well plate in a plane and making simultaneous physical sections through all the tissues, whilst retaining the experimental 96 well format.

The individual sections can be immunstained for a wide variety of biological endpoint and quantitatively analysed with automated image analysis scripts . In addition, tissue from parallel sections can be laser-dissected for transcriptomic and/or proteomic analysis to  provide complementary molecular profiling information within the same  96 well experiment.

SpheroMatrices potentiates drug development in human relevant 3D models by identifying and quantifying targets that would not be accessible with currently available platforms. To find out more, visit www.spheromatrices.com.

 

Multiplexed Immunostaining

With fixed tissue samples (SpheroMatrices and FFPE) it is possible to perform repeated cycles of Heat-induced Epitope Retrieval on  the samples, required for multiplexed staining,  without impacting upon the integrity of the tissue. With current multiplexing protocols, it is possible to stain for up to 7 tissue biomarkers providing a powerful tool for visualising:

With SpheroMatrices all treatment groups within a 96 well experiment can be assessed simultaneously, an especially valuable capability for the study of the effects of anti-tumor  drugs in  tumor/PDX models.

 

Laser Dissection Targeted (LDT) Micro Array & Pathways Analysis (LDT Arrays)

Pathology-guided LDT facilitates focused exploration of FFPE or frozen tissues , and when combined with microarray and pathways analysis can be used to explore molecular markers and pathway perturbations. The technique yields sufficient mRNA to enable  tissue region-specific unbiased pathways analysis for the identification of hits on adverse outcome pathways

An example of this approach can be found in Case Study 2.

RNAscope in situ Hybridisation (ISH)/immunostaining (IHC) and Image Analysis (ISH & IHC analysis) and colocalisation

MicroMatrices are experts in the use of RNAscope technology, capable of detecting and visualising a single RNA transcript within a cell with high sensitivity/specificity and little to no background. This technology has now been refined to allow for the detection of a single base pair change. Used in combination with immunostaining and colocalisation analysis, RNA/Basescope  offers  a unique target visualisation capacity which can guide and/or corroborate mechanistic and mode of action studies. For an example of this application, please see Case Study 1.

Whole Section Image Analysis (WSIA)

We use automated image analysis algorithms designed to quantify target/biomarker distribution, visualised via immunostaining, within pathologically defined tissue areas; data is normalised to facilitate comparison between samples.  Our WSIA flyer contains further information on the benefits of this methodology as well as a sample application.

Archival FFPE Studies for Hypothesis Generation, Mode of Action Understanding, Threshold Based Risk Assessment and Non Human Relevance (Risk assessment)

We have developed methodologies for extracting  RNA from  FFPE tissue  for use in integrated miRNA/mRNA array investigations and unbiased and focused pathways analysis. We  then further explore molecular pathology using immunohistochemistry (IHC), RNAscope in situ hybridisation (ISH) colocalisation, image analysis, etc. These combined approaches unlock the potential of archival samples and aids the design of bespoke prospective investigative studies whilst reducing the need for new animal experiments. An example of this approach can be found in Case Study 1, and also in  our white paper, produced in partnership with Zeiss.

Rescue/Repositioning

We can support in early discovery, development, and product life cycle maintenance. Should registration concerns arise as a consequence of regulatory tests with model species, MicroMatrices can assist. We will undertake mechanism-based risk assessment analyses to investigate hypotheses of toxicity and determine whether a case for non-human relevance can be demonstrated, potentially extending the commercial life of the product.

A demonstration of this approach can be seen in Case Study 1.

Biomarker Discovery/Characterisation (Biomarkers)

MicroMatrices possess a varied and adaptable toolbox of molecular profiling techniques for the discovery of novel biomarkers for toxicity  and will custom design assays to address the unique requirements of our clients. Case Study 2 provides an example of the approaches which can be used in the identification of mechanistic biomarkers within target cells.

Drug Target Tissue Mapping (Mapping)

MicroMatrices’ array of technologies are well suited to exploring and demonstrating xenobiotic targets, using both in situ hybridisation (ISH) and immune staining (IHC).  The unique sensitivity of RNA/Basescope, in particular, enables highly specific localisation.  An example of the application of this approach is contained in Case Study 3, where we demonstrate the mapping of GABA isoforms.

Reports and Publications (Reporting)

MicroMatrices will assist in the preparation and review of manuscripts for publication, study reports, SOPs, and other technical documents; please enquire.

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WE WORK WITH YOU…

on an interactive, step by step basis. Collaborations can begin with pilot projects which can then be scaled up to larger research programs, according to your requirements.